One hundred years ago, in 1909, the American Society for Clinical Investigation
(ASCI) held its first annual meeting. The founding members based this new society on
a revolutionary approach to research that emphasized newer physiological methods. In
1924 the ASCI started a new journal, the Journal of Clinical
Investigation. The ASCI has also held an annual meeting almost every year.
The society has long debated who could be a member, with discussions about whether
members must be physicians, what sorts of research they could do, and the role of
women within the society. The ASCI has also grappled with what else the society
should do, especially whether it ought to take a stand on policy issues. ASCI history
has reflected changing social, political, and economic contexts, including several
wars, concerns about the ethics of biomedical research, massive increases in federal
research funding, and an increasingly large and specialized medical environment.

One hundred years ago, in 1909, the world seemed engulfed by revolutionary ideas. Sigmund
Freud was touring the United States to lecture on a far-reaching new concept called
psychoanalysis; the architect Frank Lloyd Wright was putting the finishing touches on Robie
House in Chicago, which still looks contemporary today; Richard Strauss premiered his
operatic version of the ancient Greek tragedy of Electra, whose dissonant, lush chromatic
score still sounds modern a hundred years on; and Sultan Abdul Hamid II, the last Ottoman
sultan to rule with absolute power, was being deposed by the Young Turks, who hoped to
bring sweeping reforms to the Ottoman empire.

Radical new ideas were sweeping the biological sciences as well. Knowledge of human disease
had been reshaped throughout the 1800s by careful correlation of bedside clinical signs
with pathological autopsy findings. However, near the century’s end, creative
laboratory techniques were opening new areas for study. Investigators identified the
microbial organisms responsible for specific diseases: first tuberculosis, then many more.
Physicians applied innovative technologies in physiological laboratories to analyze organ
function in health and disease.

But most of these medical changes were taking place outside of the United States. Within
the United States, contemporary observers bemoaned the fact that “The poverty
of the resources of the medical institutions was truly pitiful” (1). The major exception to this glum landscape was the
Rockefeller Institute for Medical Research in New York City (Figure 1), founded in 1901 by the oil magnate John D. Rockefeller and headed by
the young physician Simon Flexner (whose brother Abraham, a Louisville Latin teacher, was
soon to author a report on medical education). A handful of scientists were employed at the
Rockefeller Institute to do laboratory-based research.

The Rockefeller Institute, New York City. Founded by John D. Rockefeller, the Rockefeller Institute not only symbolized a
new sort of science, it was a key early supporter of the ASCI and the
JCI. (Courtesy of the Rockefeller Archive Center.)

But there was precious little such opportunity elsewhere. Even at the best US medical
schools, professors had little use for the ideology of scientific medicine. They saw its
results as unimportant and tended at best to ignore and at worst to ridicule its findings
(2, 3).
Medical practice based on the natural sciences — so-called allopathic medicine
(the term for current MD practice) — existed in tenuous coexistence with a
variety of other fields, such as homeopathy, chiropractic, and osteopathy. At the turn of
the 20th century, it was unclear which type of medicine was destined to succeed.
(Ironically, even as he supported scientific research at the Rockefeller Institute and
elsewhere, John Rockefeller was personally averse to allopathic medicine and preferred to
be treated by homeopathic remedies; his institute — and later hospital
— was founded on the advice of one of his trusted advisers.)

In 1886 elite leaders of US medical schools had banded together to found the Association of
American Physicians (AAP). Tellingly, they also considered naming the organization the
“Association of Physicians and Pathologists” (4, 5). This alternative name
reflected their dominant model of medical research, which was firmly rooted in older,
pathology-based ideas about how to do medical research. Basing their scholarly approach on
evidence provided by postmortem pathological findings, 19th-century physicians had
effectively identified the anatomic sites of many important disease processes (6). A generation of elite American physicians had
traveled to train in Europe and then used these ideas to transform teaching and education
in a handful of US medical schools. But near the end of the century, clinicopathological
correlation was reaching the limits of its explanatory possibilities. As the 20th century
dawned, AAP members by and large remained solidly rooted in the ideas and ideology of the
previous century.

Because the AAP limited its membership, a handful of clinical investigators who worked with
newer, more innovative scientific techniques decided to strike out on their own. At 10 a.m.
on May 10, 1909, fifteen physicians, many in their early thirties, gathered at the historic
and newly remodeled New Willard Hotel in Washington, DC, to inaugurate a new society
(Figure 2). They heard an opening address by a
German-trained physiologist and physician entitled “The Science of Clinical
Medicine: What It Ought to Be and the Men to Uphold It” and then settled in to
hear twelve scientific talks. A century hence, this event does not sound all that exciting.
Yet by the standards of the day, what this group was doing was nothing less than
revolutionary. Who were these men? Why were they there? What did they accomplish? Why has
the organization they founded, the American Society for the Advancement of Clinical
Investigation (soon thereafter changed to the current American Society for Clinical
Investigation) survived — even thrived — for over a century?

The New Willard Hotel in Washington, DC, site of the first ASCI meeting in
1909. Several decades previously, US President Ulysses S. Grant used to relax in the
lobby of the Willard. People wishing to influence him would come and talk with him
there — according to one version of the history, this led to the term
“lobbyist.” (Courtesy of Willard Intercontinental
Washington.)

This article will discuss some answers to these questions. This is
“a” history of the first century of the ASCI, not
“the” history. That distinction is important, for no history is
ever complete or definitive (7). As the distinguished
scholar Christopher Hill has noted, “History has to be rewritten every
generation, because although the past does not change the present does” (8). Thinking (and rethinking) about ASCI history appears
to be an unwritten requirement for several generations of ASCI presidential addresses.
Those addresses (most of which have been published) are useful as both secondary and
primary historical sources.

Over the course of the past century, the ASCI has promoted biomedical research. It has also
been part of some of the less pleasant aspects of 20th century biomedicine. I have noted
these negative episodes, as they are clearly part of the history, but I have not dwelled on
them. At the end of the article, I consider questions that have repeatedly confronted the
ASCI over the century. This history is by no means comprehensive. There are many
fascinating but untouched questions for future historians to explore.

The ASCI started as an idea of the physician and scientist Samuel J. Meltzer, born in
1851. As a medical student in Germany, Meltzer volunteered for studies on swallowing in
which he had two stomach tubes placed in his esophagus. In the midst of one of these
experiments, the laboratory was unexpectedly visited by the Prussian minister of
education, who carefully noted Meltzer’s uncomfortable situation. Soon
thereafter, anti-vivisectionists introduced a bill claiming that experimentalists would
not dream of inflicting the same suffering on themselves as they would on animals. The
minister enlightened the legislative debate by relating his observations of
Meltzer’s role in the experiments and asking whether those advocating the
bill would be willing to put themselves in Meltzer’s place. No one
volunteered. The bill failed (9, 10).

Germany was one of the leading countries for doing medical research. But being a Jew
precluded his obtaining an academic position, and after graduation Meltzer wanted to
continue doing clinical research there. Had he been willing to convert to Christianity,
Meltzer could have pursued a career in his homeland. Instead, after several
transatlantic trips working as a ship’s surgeon, he settled in New York City
in 1885, where he practiced medicine and did physiological research during his spare
time. One can only imagine his delight when in 1904 he was asked to join the research
group at the Rockefeller Institute (Figure 3).
There he studied swallowing mechanisms and magnesium’s inhibitory effects on
muscles, studies leading to the use of magnesium to treat tetanus. He also invented a
tracheal tube for ventilating patients, an idea soon taken up by surgeons (11, 12). But
despite his many accomplishments, at the end of his career, Meltzer continued to be seen
by some as an outsider, marked by speaking the “broken English of the
immigrant” (13).

Samuel Meltzer’s physiology laboratory at the Rockefeller
Institute. Meltzer’s ideas and leadership led to the formation of the ASCI. He
emphasized the importance of not relying on older ideas of autopsy-based research,
but rather of using the latest in laboratory techniques. (Courtesy of the
Rockefeller Archive Center.)

In addition to his scientific work, Meltzer had a penchant for bringing people together.
In 1903 he founded the Society for Experimental Biology and Medicine, which is still
going strong. Some years later, as the threat of a world war loomed on the horizon,
Meltzer feared for the international fellowship of scientists. Believing that medical
men ought to promote morality, he founded a society of physicians for international good
will called Fraternitas Medicorum (14). The
society engaged thousands of members around the world, but it did not survive the US
entry into the First World War.

Meltzer was also concerned about the woeful state of clinical research in the United
States (15). At the June 1907 American Medical
Association meeting in Atlantic City, Meltzer suggested the formation of a new society
“whose prime purpose should be the encouragement of medical research in this
country by men engaged actively in the practice of medicine” (ref. 16, p. 1). In other words, this was to be a US
society for active clinicians. At follow-up meetings, the organizers decided that the
society would be limited to active investigators. Members were to be chosen on the basis
of publications in the past five years (i.e., membership was not a reward for work done
long ago); to remain eligible, members needed to remain active researchers, as evidenced
by publishing an original investigation at least once every three years.

After some organizational issues were worked out, the first annual ASCI meeting was
gaveled to order on a rainy spring day in 1909. Meltzer’s opening address
foresaw an exciting future. He warned members against spending too much time in clinical
practice, for which one would only be rewarded with a gilded tombstone. Meltzer also
stressed that contemporary clinical research should not be founded on the
“dead house” science of pathology that had characterized the
previous generation, but on the active, progressive science of physiology (17).

Follow Meltzer’s stirring words, Haven Emerson (grand-nephew of the poet
Ralph Waldo Emerson) presented the initial ASCI scientific talk, “The Blood
Pressure in Tuberculosis” (18).
Emerson’s presentation reflected an apt juxtaposition of topics. Known since
antiquity, tuberculosis had recently been brought into sharper focus by Robert
Koch’s stunning 1882 discovery in Germany of the causative bacillus. To
study patients with this disease, Emerson used a novel technology. The Italian physician
Scipione Riva-Rocci had described the first clinically useful means of measuring blood
pressure only in 1896. Emerson’s studies thus creatively applied a new
technology to a newly understood disease, a familiar investigative pattern over the
years to come. Indeed, measurement of blood pressure (Figure 4) was a central focus of four of the first twelve ASCI
presentations.

ASCI members have approached research topics by using the latest and most
sophisticated technology. At the initial ASCI meeting, the dominant new technology was the newly invented
Riva-Rocci cuff for measuring blood pressure. (Reproduced from ref. 132.)

The physicians who met at the New Willard Hotel that May day were not only friends and
colleagues, but also fellow revolutionaries. Their goal was to move clinical research
away from what they saw as a stagnating emphasis on pathological correlation and toward
a scientific basis grounded in new, more progressive sciences. Members saw themselves as
striking a blow against the established orthodoxy, much like the Young Turks of the
Ottoman Empire who were then trying to rejuvenate the Turkish Empire. ASCI members
labeled themselves the “Young Turks” and frequently used the
term to refer to themselves in their correspondence.

ASCI meetings over the next few years followed patterns similar to that of the first
one, with a move to Atlantic City in 1911. When not meeting, members were active
investigators who were required to present a paper at the meeting at least once every
three years (ref. 16, p. 7). They also had to
attend regularly; those who missed meetings without an adequate excuse were dropped from
the roll (ref. 16, p. 53).

Not much went on between meetings, save discussions about recruitment. The ASCI Council
encouraged existing members to recruit new ones, saying that “the council
cannot make nominations, and we therefore ask that each member consider carefully
whether there are not some men of his acquaintance . . . who merit election to the
society. Many clinicians well trained in scientific methods yield to the demands of
increasing practice and abandon laboratory investigations” (ref. 16, p.48). This warning reflected the increasing
appeal of full-time clinical practice in an era in which the practicing
physician’s status (and income) was rapidly increasing (a danger Meltzer had
noted in his inaugural address).

By its 1914 meeting, the ASCI had enrolled more than 70 members. The increasing size
forced the first length limits on presentations: ten minutes for the talk, five minutes
for discussion. Papers for oral presentation also started to be limited to only the
first 30 titles submitted to the secretary (cut down to 25 in 1916) (ref. 16, pp. 74, 78). Papers were accepted simply on a
first-come, first-served basis until 1922, when the Council decided, “owing
to the fact that the present way of making up the program does not always lead to the
best selection,” to leave selection of papers for presentation
“to the discretion of the president” (ref. 16, p. 235). Also in 1914, not for the last time, a change to the
meeting format was proposed. Meltzer suggested a multiple-day meeting so that more
members could present a paper, saying the ASCI need not act like an appendix to the
“older Association of American Physicians.” His suggestion was
not adopted. The original name was thought to be too unwieldy and in 1916 was shortened
from the original American Society for the Advancement of Clinical Investigation to
simply the American Society for Clinical Investigation over the other suggested
designation, the “American Society of Internal Medicine.”

The First World War started in Europe in 1914; the United States formally entered the
conflict in 1917. It hit medical schools hard. George Blumer of Yale University devoted
his 1918 ASCI presidential address to “Medical Education in Relation to the
War.” His presentation was noteworthy for at least two reasons. First, he
spoke publicly and forcefully on matters of public policy — and the question
of whether and how the ASCI should advocate policy positions would continue to be
debated throughout the century. Second, his concern over threats to the
“very existence of the schools” speaks both to the broad-based
impact of the war and the precarious nature of the newly reformed medical schools. The
war ended later in 1918, and the next year, members were cautioned not to let the
disorganized postwar environment curtail their “investigative
spirit” (and advised against joint authorship) (19, 20).

Both the medical schools and ASCI thrived in the postwar period. Being elected to the
ASCI meant more than merely an honor to be listed on a vita. Members looked forward to
socializing at each annual meeting, to listening to others’ talks, and to
hearing useful criticism of their own work. Physicians came to see the ASCI as their
first choice for presenting a paper. The AAP was a second choice, to be used only if the
paper was not going to make it onto the ASCI program (21).

ASCI meetings were held on the eastern seaboard. Because the time and money required for
train travel posed a difficult or insurmountable obstacle to many clinical
investigators, particularly those who lived in the interior of the country, ASCI
President Leonard Rowntree suggested in 1921 that it might be a good idea to form local
societies, especially for younger investigators (22). But the next year, an ASCI committee said it was
“inadvisable” to establish branch societies, opining that in all
large cities, there are “medical organizations in which the young man in
internal medicine may become a member and thus obtain the stimulation which arises from
contact with others.” Instead, the committee urged ASCI members to stay in
touch with younger men of special promise.

Perhaps the answer was not branch societies but a new society. A group of 12 midwestern
physicians (7 of whom were ASCI members) met in 1919 to consider ways to overcome the
geographical difficulties. After prolonged discussion, in 1927 they wrote to the ASCI
about their desire to form a new society. Ernest Irons, who as an intern cared for the
first patient described with sickle cell anemia and who soon was to be dean of Rush
Medical College, explained that “the point was to give the younger men in
the middle West a chance to read their papers and get the benefit of criticism as well
as the honor of getting into the society.” In no way was this intended to be
a rival society. The ASCI Council replied that the “foundation of a new
Society had the best wishes of the American Society for Clinical Investigation, but that
the latter did not want to participate actively in its formation.” The
Council went on to say that it “heartily endorses this move and recommends
that the Society extend its best wishes for the immediate success of the new
society.” The first formal meeting of the ASCI-inspired Central Society for
Clinical Research was held in 1928 in Chicago. For almost two decades, the ASCI
published the Central Society meeting abstracts in the Journal of Clinical
Investigation (JCI), a new journal to whose creation we now
turn (23).

The year 1924 saw the establishment of the JCI. As early as 1916, ideas
about such a journal had been floated to the board of directors of the Rockefeller
Institute, but nothing was done. In 1921 the director of the Rockefeller Institute
Hospital, Rufus Cole, sent the board a detailed 14-page memo explaining the rationale
for establishing a new journal (24). He pointed
out the need to encourage clinical investigation, noting that “relatively
few consciously organized scientific investigations of medical problems have been
undertaken in our university departments of medicine or by men trained in the study of
disease at the bedside.” Part of the problem was that people who did
clinical research had a hard time finding an appropriate journal in which to publish.
Well-established clinical research journals existed in other countries, such as Germany,
France, and England. But in the United States, while the Rockefeller-supported
Journal of Experimental Medicine provided an outlet for pure
laboratory work, there was no good place for people whose primary goal was the
“control and cure of disease” to publish their work. Cole
claimed that “there would be no serious lack of material to supply a journal
of the character proposed,” listing several universities doing work that
could be published in a new journal and asserting that papers from the hospital of the
Rockefeller Institute alone over the past 10 years could fill nine volumes. No action
immediately followed this 1921 memo.

Two years later, the noted internist and dean of Vanderbilt University Medical School,
Canby Robinson, wrote to the Rockefeller Institute Director of Laboratories (who was in
actuality functioning as the overall director), Simon Flexner, noting that
“clinical investigation has been rapidly developing in this country, largely
due to the great impetus given to it by the Hospital of the Rockefeller Institute . . .
There is at present no journal properly expressing this important development in
American Medicine. There is not only a great delay in publishing, but also a scattering
of material into journals designed for other special groups of workers.”
Robinson went on to say that a new journal could “serve as a stimulus for
the elevation of the standards of clinical investigation.” If the
Rockefeller Institute didn’t want to publish such a journal, possibly they
could support the ASCI to do so (25). When the
Institute was slow to support the journal, Robinson again wrote to Flexner on March 25,
1924, to say that he had made inquiries to other publishers about publishing such a
journal, including Williams and Wilkins and the University of Chicago Press (26).

Perhaps this letter stimulated the Board of Scientific Directors to come to a decision.
On April 26, 1924, the Board decided to support a journal and recommended a yearly grant
of $3,000 to the ASCI, available for three years, “by which time it is
expected that the Journal will be self-supporting.” In a burst of optimism,
the board stipulated that if the journal became self-supporting before then, the ASCI
should not take the entire grant. The first issue of the JCI came out
October 24, 1924, a new journal led by “new men, trained in a new way . . .
being supplied with new hospitals properly equipped with laboratories”
(27).

JCI founders anticipated a flood of papers and an eager readership. But
the reality of the first decade was far more sobering. Editors found themselves
desperate for submissions. Alfred Cohn wrote a colleague in December 1925 saying that
“We are much in need of material for the Journal of Clinical Investigation.
The February number should go to press on January 1st and at present we have only two
papers. I should be glad if you could direct any good papers to us” (28). The paucity of submissions forced the editors
to publish a “large majority of the papers that had been
submitted.” Nor did the annual ASCI meeting supply the anticipated number of
papers; only 10 of the 57 papers on the 1925 program were submitted. In 1927 the
JCI was still accepting 71% of the papers it received (29).

One response to the lackadaisical submission rate was to not commit to a set publishing
schedule and to publish only whenever an adequate number of papers was in hand. This was
not an unprecedented approach — the British physician Sir Thomas Lewis had
originally adopted it for his prestigious journal Heart, which had
started publishing in 1909. At one point, JCI editors decided
“to continue issuing volumes at a rate depending upon the available material
(600 pages per volume) not to exceed 2 volumes per year” (30).

Not only did they receive few submissions, but the demand for the JCI
was far less than expected. Robinson wrote to Flexner after two years, in 1926, saying
that they needed 1,000 subscribers to break even but had only 319, lamenting that
“the spread of the Journal has been very slow” (31). Even in these early days, some questioned the
clinical relevance of JCI articles. As editors reported to the ASCI
Council in 1930, “The recognition of the value of these articles by
physicians at large in our country must inevitably, however, take much more time and can
probably be expected only after the practical results of such studies become
demonstrated.” A flood of subscriptions from such physicians was unlikely to
happen.

Who should bear the financial burden for this struggling journal? While the Rockefeller
Foundation was willing to assume start-up costs, foundation officials believed that
universities needed to assume some of the ongoing costs, that “every
university department should have an item in its budget for the cost of publication of
research data . . .” (32). In January
1928 the Rockefeller Institute provided the ASCI with a final installment for the
JCI and advised the Council that further support would not be
forthcoming.

The JCI was able to improve its financial situation. Although they did
not formally budget for publication costs per se, about 15 university
clinics signed up as associate members to provide a few hundred dollars a year. A dues
increase for individuals from $3 to $10 per year garnered some additional funds, as well
as providing each ASCI member with a subscription to the JCI. In 1930,
just as the Great Depression was getting started, the JCI editor could
report to Council that for the first time the journal was wholly supported by
subscribers and university clinics.

But because university support was pledged on only a year-to-year basis, and because of
a desire to improve business management, the ASCI approached the Chemical Foundation for
support. The Foundation took over running the JCI on July 15, 1931,
just as general economic conditions worsened. In 1933 the JCI had only
577 subscribers. Editors tried to increase subscriptions by mailing information to
potential subscribers. This effort cost over $1,300, yet in the face of the Great
Depression yielded only three new subscriptions at $10 each. The manuscript acceptance
rate remained well above 50%. The Chemical Foundation soon found itself subsidizing an
annual deficit of almost $4,000 per year (almost $70,000 in 2008 dollars). They were no
more sanguine than the Rockefeller Institute had been about remaining indefinitely the
primary source of long-term support. According to the JCI editor, they
“indicated to us that a journal to receive continuing support must be
progressing towards a self-supporting basis. It is impossible to contend that under our
present policies our journal is exhibiting satisfactory progress towards
self-support.” Self-support would require about 900 subscriptions, and the
editor was pessimistic about getting there. “The practically complete
failure of three vigorous advertising campaigns leads me to infer that it is useless to
expect the necessary increase in subscriptions.” He outlined the options.
The ASCI could drop the price to $4 per year and hope to get 2,500 new subscriptions.
They could attempt to broaden the journal’s appeal by adding review
articles. They could institute page charges, publish only abstracts, or improve
management. Or, once bank reserves were exhausted, the JCI could simply
cease publication sometime around December 1935. In other words, in the mid-1930s, the
editors seriously considered the possibility that the journal might fold (33).

But somehow, the editors managed, barely, to keep the journal intact until economic
conditions improved. One editor reflected “That a journal should survive its
preliminary stages must often have been a source of wonder to its sponsors . . . The
Journal has never been prosperous in any ordinary meaning of the word. Its financial
life has always been precarious” (34). The Chemical Foundation eventually withdrew support in 1940, but by then
the JCI was well-enough established to carry on.

During the interwar years, the annual ASCI meetings started to be seen as important news
events. In 1926 the New York Times noted that the ASCI meeting would be
“turning the Hotel Traymore into a clinical laboratory” (35) (Figure 5).
Sometimes reporters covered scientific studies that we would now see as progressive,
such as using radium to measure blood velocity; other times they covered research
results that we would not see as accurate today, such as the claim that
“heart burn” was not due to acid or any other physical
substance, but to local dilation of the digestive tract (36). When barred from scientific sessions, reporters made their pique clear,
complaining that “the conservative medical men decline to make public the
nature of developments reported, except in professional publications.” If
nothing else, this sort of commentary reflected the fact that what the ASCI was doing
had become a topic of national interest. (Nearer to the end of the century, the lack of
advance information to journalists again made the papers, only this time because of the
impact on the stock prices of biotech companies! [ref. 37]).

The Traymore Hotel was the site of many ASCI meetings in Atlantic City. The ASCI no longer meets in Atlantic City, and the Traymore Hotel was demolished
in 1972. (Reproduced with permission from the New York Public Library.)

As had been the case since the very first ASCI meeting, new technologies often took
center stage. Enamored of the new “atomic forces” being
unleashed, scientists claimed that neutron rays were more powerful at treating disease
than X-rays, at least in mice (38, 39). In 1939, with war clouds gathering over Europe,
a young Harvard anesthesiologist got top media billing for measuring anesthetic effects
with another new technology, the EEG (40, 41). This was not the last time that Henry Beecher
was to be in the news.

In 1941 the United States entered the Second World War, a war that impacted on every
facet of civilian life. ASCI leaders adjusted dues and waived attendance requirements
for members engaged in the war effort. Federal officials asked that “unless
the meeting had a direct bearing on the war effort, it would be appreciated if it were
omitted in order to lessen the burden on transportation facilities,” and the
ASCI national meetings of 1943 and 1945 were canceled.

Still, the JCI continued to publish. In 1942 manuscript reviewers
started to include experts not on the editorial board, thus emphasizing that the
“Journal is the organ of the whole Society.” Many
JCI papers were related to the war effort; the entire July 1944 issue
was devoted to research on plasma fractionation, a key technique for treating wounded
soldiers. Much of this work was being done under contract from the federally funded
Committee on Medical Research; publication of war-related research was supported by the
Commonwealth Fund and the Macy Foundation. Concerned that “The war has made
it impossible to send the Journal to many parts of the world” and
“An unknown number of copies have gone to the bottom of the
ocean,” JCI editors anticipated the need to reprint back
numbers after the war.

When peace finally came, it was clear that scientific research had played a major role
in determining the victor (Figure 6). This was true
most obviously for the physical sciences, which developed radar and the atomic bomb, but
it was also true for the biomedical sciences, which developed blood banking techniques
and the mass production of penicillin. But in terms of the impact of the war on medical
research, arguably even more important than the wartime scientific advances was a
transformational set of organizational decisions that would shape the next 50 years of
biomedical research (and beyond). The ASCI and its members reflected and debated these
decisions and wound up benefiting beyond their wildest dreams from this radical change
in the support of scientific research.

Prior to 1940, the federal government supported very little biomedical research, almost
all within federally run institutions. But from early in the Second World War, it was
clear that science would play a major role in the war’s outcome, that the
federal government would need to support scientific research, and that existing federal
laboratories lacked sufficient capacity. Therefore, in 1941 the Committee on Medical
Research started supporting research projects all around the country. And, given what
amounted to a direct presidential mandate and virtually unlimited funds, they funded
generously. Scientists became accustomed to having ample resources for whatever they
needed to do. This was a new way of doing research, and one to which scientists found it
easy to adapt. Clinical researchers produced impressive results on topics such as
antibiotics, adrenal steroids, and blood plasma. Congress saw these results as an
impressive harbinger of what biomedical researchers could accomplish if only given
adequate resources (42).

Funds were provided through the mechanism of research contracts, which had clearly
defined objectives and required quarterly financial and scientific reports. Until 1944,
the Public Health Service (PHS) lacked legislative authority to award extramural grants.
But the PHS Act of 1944, little noted at the time, authorized the Surgeon General,
rather than relying only on contracts, to “make grants in aid to
universities [and] hospitals . . .” After the war’s end, 44
research contracts were transferred to the PHS (43). Many of those projects used the newly available antibiotic penicillin.
Because the cost of penicillin was rapidly falling, additional funds became available,
and in 1945 the PHS advised medical school deans that they could submit letters asking
for additional research support. With this rather indirect approach, a system of
extramural PHS research grants came into existence.

It was hardly the federal research system envisioned by Vannevar Bush, who had directed
the wartime Office of Scientific Research and Development. In a report for President
Franklin Roosevelt, Bush advocated a massive increase in postwar federal research
support. He argued that “basic scientific research” was
essential for national security, economic growth, and the very values on which the
United States was based. As we could no longer depend on “ravaged Europe as
a source of fundamental knowledge,” Bush proposed a single overarching
national research foundation that would encompass all forms of scientific research,
including medical research (44). However, for a
variety of political reasons, that agency, the National Science Foundation (NSF), was
not created until 1950. By then, the extramural PHS program was already so well
established that the new NSF decided to leave biomedical research funding to the PHS
(45, 46).

PHS extramural funding grew more than ten-fold in the first four years after the war and
continued to grow rapidly thereafter. Faced with decisions about how to distribute these
funds, the PHS invented now-familiar systems. They appointed civilian consultants to
“study sections” to advise about grant funding. Disease-oriented
institutes were established, and the grant-making structure reflected those divisions.
The funding system has continued in basically the same form to the present day, albeit
at a scale that likely would surprise even the most ardent advocate in 1945.

ASCI members flourished in this new system. However, as natural as the grant-making
system may seem in 2009, it was initially quite controversial. Logical, rational
opposition was raised to federal support for research. The main questions were whether
the risks outweighed the benefits and whether funds ought to be allocated to individual
investigators or to some larger unit.

Thomas Francis titled his 1946 ASCI presidential address “Biological
Beachheads,” doubtless with some thought to the recently ended conflict
(47). He was skeptical about creating a new
national agency for research support because “Administrative principles of a
large organization tend to be founded on orthodoxy.” Rather than having
investigators waste time and divert their attention from important scientific work in
order to seek funds, he thought it better to have general research funds distributed
through universities. Francis warned about the “red tape of premature
accounting and justification” and about the role of lobbying and pressure
groups. But at the root of his and others’ concerns was an arguably even
more serious set of issues. The medical research atrocities committed in Germany during
the war were starting to become widely known. Many of these atrocities had been
committed by extremely distinguished physicians, clinical scientists who prior to 1939
would have been considered among the very best in the world. How, Americans wondered,
could such distinguished physicians have committed such heinous acts? The answer was
thought to lie, in part, in the government support of their research. The events in
Germany were thus seen as an example of what could happen when the government gets
involved in research support.

But confidence in the ethical sensibilities of American clinical scientists combined
with the promise of readily available funds quickly overcame such concerns. In October
1949, ASCI member John H. Dingle, recently named head of preventive medicine at Western
Reserve University, wrote to incoming ASCI president Thomas Hale Ham (of the
Ham’s test, the definitive test for diagnosing paroxysmal nocturnal
hemoglobinuria [PNH]). Dingle had represented the ASCI on the National Research Council
and had already advised the ASCI Council to take more interest in the workings of
federal support. In his letter to Ham, Dingle shared concerns that the widespread
provision of federal research grants meant the “possibility of governmental
control and ultimate political domination” and that “control of
funds may be in the hands of a small number of individuals who might thus acquire
tremendous power.” However, he made the prescient observation that the ASCI
“must accept the reality of government funds for research and
education,” for “governmental funds, chiefly federal, as a means
of support of research are of great importance and probably will continue to be
so” (48). Ham was to warn the next
year of the dangers of choosing a research problem based on ease of financial support,
and especially of politics (49).

But before long, the question about whether government funds were to support research
had been answered in the affirmative. The question remained (if only for a while): How?
Funds might have been awarded to the promising investigator absent any specific research
plan. This method could avoid what some ASCI presidents saw as the “wasteful
expenditure of large sums of money” on the assumption that
“scientific knowledge can be bought”; the money would be better
used not for specific research projects but to fund individual endowments, offered to
“the man and not the project” (50, 51). Another possibility, one that
was for a time close to the standard, was for funds to be given not to the investigator,
but to the university or to the head of a unit. In 1948, JCI editors
could still assert that “It is taken for granted that the head of a
department is responsible for acquiring the funds for a particular study”
(52). But the burden soon shifted from
department heads to laboratory directors, who took the first steps toward becoming
administrators and grant-getters. By 1956 ASCI president A. McGehee Harvey lamented that
older investigators do not spend enough time in the laboratory. His solution was more
federal money for unrestricted general support and less for categorized research (53). Albeit more for categorized research than for
general support, federal funds kept on flowing.

The 1950s marked the start of “American Medicine’s Golden
Age,” and the ASCI was very much a part of it (54) (Figures 7 and 8). The spigots of NIH funding opened ever wider; many
new medical schools were opened; rapidly expanding Veterans Administration hospitals and
laboratories offered new opportunities for research and training; and the
public’s already high opinion of physicians became even higher (55). The public read about ASCI meetings in glowing
terms: “Researchers Cite Medicine’s Gains,” read one
headline, followed by an opening sentence stating that “Medical researchers
had a field day against disease and infirmity . . .” as they heard reports
that “delineated the frontier of medical science today” (56). Perhaps the height of praise came in a 1952
Time magazine article entitled “The Young
Turks.” The reporter observed that in the youthful audience,
“there was not a greybeard in the lot,” noting that the lead
speaker was “Tall and as slim as in undergraduate days” as he
“walked to the dais with an athlete’s loose-jointed
stride” to speak on the future of medical research (57). Even though they drew a public spotlight, ASCI meetings
remained, for a time, what they were at the start — an intimate gathering of
close friends. Scientific discussions would spill out of the meeting room and onto walks
on the famous Atlantic City Boardwalk or into a bar and dinner-time socializing.
Up-and-coming postdoctoral fellows invited by their laboratory directors would learn,
quite literally, at the knee of accomplished, senior members (58, 59).

As federal funding for laboratories expanded, more and more of ASCI
members’ research came to be done not on human beings but on
laboratory animals, such as this Norwegian rat in a photograph from the 1950s. (Courtesy of the National Library of Medicine.)

But the meetings existed as part of a larger, changing context. Especially in a country
as large as the United States, transportation is critical to the workings of any
national society. As long as trains and cars remained the primary mode of travel,
geography remained a limiting factor. As recently as the 1930s the argument was made
that a JCI editor really ought to live in New York City, but in any
event could not live any farther away than Boston or Philadelphia (60). But after the Second World War, airplanes replaced trains, and
a speaker could note that “The ease and speed of travel and the availability
of funds to support it has led to such a massive proliferation of meetings, conferences,
and symposia that one wonders when the participants will find the time to get any new
work done” (61). ASCI meetings grew
enormously. These meetings had long been held with the AAP; with the addition of the
American Federation for Clinical Research (AFCR, created in 1940, which changed its name
to the American Federation for Medical Research [AFMR] in 1996), the so-called
Tri-Societies meetings came routinely to draw combined attendances in the several
thousands.

As a result, in 1950 the meetings moved from a relatively small Atlantic City hotel to
the Steel Pier Theater and a much larger auditorium. While the new site allowed more
trainees to be inspired by the academic elite’s presentations, some members
complained that the meetings had become too large, too crowded, and the discussions less
intense and less productive. Nonetheless, these large meetings became the defining
events of the academic year. Trainees were expected to go. Physicians made long-lasting
reputations and secured excellent jobs based on their ASCI presentations. The most
exciting research of the year was presented there; “medical history was
being written” (62, 63).

As the meetings grew, they became more formal. ASCI members sat in a special roped-off
section, first formally noted in the 1941 program, “where the lions of
academic medicine were loosely caged” and were the only ones allowed to ask
questions (64). Eugene Braunwald has provided a
vivid description of the attendees: “Virtually all who strolled by,
regardless of age, were white males, usually with closely cropped hair and wearing a
standard uniform: white shirt with button-down collar, striped tie (black and dark green
were the favorites), charcoal gray slacks, herringbone jacket often with leather elbow
patches, and well-shined black shoes. Almost all . . . were pipe smokers”
(65).

In 1959, as the ASCI celebrated its 50th anniversary, the future appeared secure for the
values that the ASCI advocated (66). Federal
support for clinical research was no longer seen as something to be debated. Rather, the
public had come to believe that “their future depends on scientific
research,” and public funding, rather than being controversial, was thought
to be virtually guaranteed (67). Over the
preceding 20 years, federal grants for medical research had risen from $40 to $700
million per year and had become the dominant source of support for medical research
(68).

Yet all was not rosy. Some rough spots might have seemed foreseeable to those who
earlier had warned that federal research funding could be used as a political tool. ASCI
members confronted the Cold War bigotry of the McCarthy era. Laboratory directors were
pressured to fire staff who belonged to the wrong type of organization (69). ASCI members were dismissed from study sections
after anonymous accusations of disloyalty (70).
Grant funding could be used as a tool for political pressure, leading ASCI members in
1955 to send the following statement to the secretary of Health, Education, and Welfare:
“We . . . are greatly perturbed by your recent announcement that competent
investigators have been deprived of USPHS research funds because of allegedly derogatory
information in their files. We recognize the need for security clearance of individuals
engaged in classified research. However, it is our firm belief that awarding grants for
unclassified research on any basis other than the value of the project and the
competence of the investigator endangers not only scientific freedom but also the very
foundations of our way of life.” During the Cold War, the spread of science
was increasingly restricted by ideological pressures; while the JCI
once had more than 100 subscribers in China, by 1956 it had only two.

The ethics of clinical research was thrust into the spotlight with ASCI member Henry
Beecher’s landmark 1966 New England Journal of Medicine
article “Ethics and Clinical Research,” in which he described
serious ethical issues in 22 experiments (71).
Though the experiments were not specifically cited, Beecher’s examples were
prominent enough studies by distinguished enough clinical scientists that contemporary
readers had little doubt as to the identity of many of the investigators (72). Of the 22 papers, at least seven had authors
who were ASCI members, and three had been published in the JCI.
Beecher’s article sparked a flurry of national attention. An ASCI committee
met with representatives of several other major societies to discuss the 1964
Declaration of Helsinki, a statement of ethical principles proposed by the World Medical
Association. The ASCI endorsed the Declaration and published it in the
JCI (73). In 1967 ASCI president
Grant Liddle devoted his address to the ethics of clinical investigation (although he
preferred the term “mores”) and to the Declaration of Helsinki,
giving a detailed analysis of why and when informed consent might come into conflict
with other principles (74). Liddle also suggested
that clinical investigators ought to form a moral community with its own responsibility
for enforcing a code of conduct. Although he did not mention Beecher explicitly,
it’s hard to believe that Liddle’s talk was not in some
important ways a response to Beecher’s exposé.

The 1960s were turbulent times. In his 1964 presidential address, Irving M. London noted
the “revolts of the colored peoples of the world against deprivation and
indignity” (75). Meanwhile, the US
military was moving ever more deeply into a controversial conflict in Southeast Asia. In
1970, as conflicts over the Vietnam War convulsed American society, the controversy
spilled over into the Atlantic City meetings. ASCI member Kurt Hirschhorn proposed that
the following message be communicated to President Richard Nixon: “The
American Society for Clinical Investigation condemns the increasing US military
involvement in Indochina because of its destructive effects on the health and welfare of
the people of both the United States and Indochina. We believe that the funds expended
for this effort would be more beneficial if used to improve the health of both peoples.
We therefore urge you to reverse the recent decision increasing the scope of US military
action in Indochina.” This resolution was put to a secret ballot
— not on whether the members agreed with the expressed sentiment, but on
whether to send this message to Nixon. The vote was 102 to 150 against sending the
message. However, this vote made it clear that a significant proportion of the voting
membership wanted the ASCI to take a public stand on at least some national policy
issues. The question of ASCI involvement in policy discussions was to come up again.

The upheaval over Vietnam was soon followed by debacles such as the Watergate scandal
and the Three Mile Island accident, leading to increased public distrust of many
previously respected institutions. Concerns about science were fueled by a few prominent
instances of fraudulent scientific research, some presented at the ASCI annual meeting.
One of the most prominent examples was offered at 2:00 on the afternoon of Monday, April
30, 1973, with the auspicious title of “Successful Tissue and Organ
Allotransplantation without Immunosuppression.” The results were so striking
that the author was given a prolonged standing ovation (William N. Kelley, personal
communication). This may have been the only such standing ovation ever given at an ASCI
presentation. Unfortunately, the results were found all too soon to be invented (76).

Worried that the handful of known fraudulent cases was merely the tip of the iceberg of
a much more systemic problem, the US Congress held hearings in 1981 on publication of
fraud in biomedical research (77). Chaired by
Representative Albert Gore Jr., the hearings attracted widespread attention (78, 79). The
JCI became a prominent part of the public discussion because one of
the fraudulent cases investigated by the committee had appeared in the
JCI. When the article’s senior author became aware that the
work was fraudulent and wanted to publish a retraction letter, the editor refused to do
so because the JCI had a “tradition of publishing only
original scientific work” (which had been a point of pride at the 50th
anniversary) and had never before had a correspondence section. The JCI
editor’s letter of May 28, 1980, refusing to publish a retraction was
included in the Congressional report as well as being quoted in the New York
Times. The JCI’s position received no support;
most felt that the recent revelations of misconduct precluded a “business as
usual attitude.”

The JCI soon broke with its previous tradition and started publishing
retractions (80). The issue of fraud was salient
enough to be the topic of the next year’s ASCI presidential address by
Philip Majerus (81). In his years as
JCI editor (1977–1981), Majerus said that he saw dozens of
examples of inappropriate data interpretation but found only two cases of fraud.
Unfortunately, the JCI was once again in the national press over
fraudulent articles only a few years later (82).
Issues surrounding appropriate publication continue to arise, albeit with a more open
discussion than had been the case in the 1980s (83).

Throughout the 1960s and the 1970s, the combined spring meetings of the ASCI, AAP, and
AFCR were the jewel in the crown of the academic clinical researcher. A presentation
there could be recalled later as the key moment in an early career (84). Yet the glory years could not continue. The
days of the 3,000- to 4,000-person mega-meetings were numbered. The precise turning
point is hard to say. Perhaps it was about the time the meetings left Atlantic City, in
1977. Perhaps it was 1985, when the number of submitted abstracts started to fall. In
any event, the decline, when it came, was rapid. The number of abstracts had fallen by
almost half in 1992, and by 1996 attendance had fallen by a similar percentage (85, 86).

The demise of the mega-meeting had several interrelated causes. One was the same
efficient transportation that had enabled its rise only a few decades before. Just as
airplanes could carry an investigator across the country to the spring meetings,
airplanes could just as easily carry that same investigator somewhere else. Previously,
traveling overnight (or two nights) on a train represented a significant time investment
and encouraged travelers to settle in for an extended stay. No more. Now, air travel
made it easy to travel and return in a single day. Professors found themselves flying
around the continent year-round to give seminars, to collaborate, to consult, and to
engage in the sorts of face-to-face interactions that had previously been the unique
staple of the spring Atlantic City meetings. Junior scientists were less likely to
travel than their senior mentors, and the demise of the meetings meant they experienced
less of the informal, cross-institutional mentorship that previously had been obtained
on a walk down the Boardwalk.

Just as the airplane could take someone to visit another institution, so, too, it could
take someone to attend a different meeting. Probably the most important single factor in
the demise of the Tri-Societies’ mega-meeting was the inexorable rise of
medical specialties and subspecialties. This change had been a long time coming, and it
did not come easily. The clinical researchers who had created the ASCI espoused an
aggressively generalist style, actively opposing any hint of specialization. Consider
the intensity of Alfred Cohn, an early ASCI member based at the Rockefeller Institute.
Cohn was a leading ECG researcher and highly respected expert on heart disease. Yet he
railed against the very existence of a special journal on heart disease: “I
am quite frankly opposed to the founding of journals devoted to the study of specific
viscera. It seems to me that the study of heart disease from 1909 onward [the founding
date for the journal Heart] lost a great deal of significance on
account of its divorce from the main current of clinical medicine while the study of
medicine itself was deprived of proper contact with the development of knowledge in this
field by publishing good things in separate journals. In a sense the tendency is created
for fellows who work on heart disease to study no other journals . . .”
(87).

Cohen’s concerns notwithstanding, the field of cardiology and its journals
continued to grow. At least for a time, cardiology remained firmly imbedded within
internal medicine (although cardiology fellows doubtless gravitated to reading heart
disease journals). And it is internal medicine that has long dominated the ASCI, though
membership is open to all specialties. (Consider that the other name considered for the
1916 name change was the “American Society of Internal
Medicine.”)

Prior to the Second World War, it might have been possible to hold fast to the belief
that internal medicine could continue as a single, unified specialty. During the war,
the Army’s Medical Department emphasized specialty care. Given the massive
size of the Medical Department and the numbers of physicians involved, the Department
provided a big impetus toward the dominance of specialty and subspecialty medicine
(88). After the war, the nascent cracks
between subspecialties started to become too obvious to ignore. New specialties arose,
based increasingly on the new technologies that were coming to dominate and define
biomedical research. ASCI president Carl V. Moore noted the tendency of modern
laboratories to have “more pieces of equipment than ideas”
(89). New specialty boards were formed. In
1952 ASCI president W. Barry Wood made the prescient observation that specialization is
here to stay (90).

Yet for a while, internal medicine departments did not embrace subspecialization. The
average department size in 1957 was a scant 15 faculty members, a group small enough to
easily remain unified. Even as NIH funds continued to grow exponentially, department
chairs remained generally oblivious to the upcoming explosion that would make a unified
department difficult to maintain. Chairs in 1957 hoped that 15 years hence, in 1972,
department size would modestly increase, but only to 32 faculty members (91). The actual increase in departmental size was
not imagined by “anyone in academia,” even by those at the most
prestigious schools (92). In fact, surging NIH
funding led to not only larger but also more subspecialized departments with larger and
more autonomous division, especially cardiology, gastroenterology, and hematology (93). As internal medicine subspecialties grew, they
assumed the usual trappings of a separate specialty: journals, certification,
reimbursement, and, most important for this discussion, separate meetings. As
departments of internal medicine became ever bigger (even by 1972, a department of 32
would have seemed small), there was less communication between divisions, less interest
in being a single, unified group. Internal medicine departments became fragmented based
on topic, on size, on earning power (94, 95). Subspecialties became the center of the
academic universe, and the number of attendees at subspecialty meetings swelled to as
many as 30,000. Faculty and trainees increasingly went to such meetings to present the
newest, hottest research results.

What was to be done with the ASCI meeting? Except for a couple of wartime years (1943
and 1945), there seems to have been a consistent consensus that an annual meeting ought
to be held. Debates about the form and content of the annual meeting have been a
constant almost since its inception. Should there be a two-day session? Rejected in
1921. Should there be an evening session? In 1932 this question was raised —
and after considerable debate, the answer was no. Should there be separate, specialized
sections during the annual meeting? Sometimes, but not usually. These scheduling
experiments were dismissed in favor of plenary sessions, in the name of unity, in the
belief — usually valid in the prewar era — that members would
want to remain current across the broad swath of disciplinary perspectives.

Should ASCI meetings always be held in the same place? Starting in 1933, the ASCI met in
Atlantic City for many years, but not without discussion of change. The 1954 Council
noted that always meeting in the same place causes “disadvantages and
inequities to a large segment of our membership and guests” and the next
year noted that “the society will continue active [italics
in original] exploration of the possibility of meeting occasionally in a city other than
Atlantic City.” But it would be 1977 before the meeting left Atlantic City
and moved to Washington, DC, starting what ASCI president Laurence Early called an
“annual sojourn around the continent” with the sister societies
(96). As attendance dropped and the most
exciting scientific findings moved to subspecialty meetings, there was no longer the
need or the desire for the same type of massive Tri-Societies meeting. In 1998 the ASCI
held its final meeting with the AFMR. After the breakup, there were some attempts made
to reproduce the spirit of a joint meeting with other clinical groups, none with
significant success. The meetings today are held with the AAP and are focused on longer,
thematically linked talks by distinguished scholars. The question as to what sort of
annual meeting to hold has been a constant debate over the ASCI’s history,
and it will doubtless continue.

ASCI members have had to answer many other questions over the past century. While the
questions may not change, the answers have. Or not. Some questions raised over the
course of the century have been essentially resolved — should physicians do
clinical research (yes), should the ASCI formally sponsor local societies (no), should
the association publish a journal (yes), should its members rely on federal research
funds awarded on the basis of individual research grant applications (yes). These were
all questions that could have been answered differently. On the other hand, debates over
some core questions have persisted over many decades.

One of the most fundamental questions for any organization is simply this: Who can be a
member? The ASCI was founded by physicians, for physicians. But what about people doing
what is clearly clinical research of the highest quality but who do not hold an MD? This
question was called early on for a very high-profile candidate.

In 1924 the ASCI decided not to admit the Toronto physiologist J.J.R. MacLeod. This
rejection was special enough (indeed, it seems to be unique in this regard) that the
Council instructed the secretary to write a personal note to MacLeod
“expressing the regret of the society that not without modification of the
Constitution of the Society would it be possible to add his name to the list of
members.” For MacLeod was no ordinary nominee. Along with the surgeon
Frederick Banting, he had discovered insulin, one of the most dramatic and important
medical discoveries of the 20th century. Soon after the discovery, there began a
life-long controversy over who deserved credit, a controversy only heightened after the
1923 Nobel Prize in Medicine or Physiology was jointly awarded to Banting and MacLeod
(historical scholarship has made it clear that both were undoubtedly worthy of the
prize; ref. 97). MacLeod held a PhD, but no MD.
As accomplished as MacLeod was, and as important as his discovery was, there was to be
no wiggle room on the requirement that members be physicians. Even if he be a Nobel
laureate, MacLeod could not be an ASCI member. Banting, on the other hand, was promptly
honored with ASCI membership upon his initial nomination in 1924.

The MD requirement has persisted, although another original membership requirement has
gradually slipped away. Early on, the ASCI was quite explicit that members needed not
only to hold an MD, but also to be active, practicing clinicians. On more than one
occasion the Council, not wanting to elect someone who was “not primarily
interested in the clinical branch of medicine,” asked the secretary to
explicitly seek assurance from nominators that a candidate was engaged in active
clinical practice (ref. 16, pp. 225; and ref.
98). Over the years, this clinical practice
requirement gradually disappeared without any formal debate being recorded. By the time
Henry Kunkel gave his 1962 ASCI presidential address, “The Training of the
Clinical Investigator,” it was clear that many ASCI nominees had little, if
any, regular contact with patient care (99).

As “clinical research” moved farther from the bedside and closer
to the laboratory bench, it became increasingly apparent that the research being done by
people holding MDs and people holding PhDs (but no MDs) was often very similar. In 1979,
dropping numbers of nominees led ASCI president Kenneth L. Melmon to consider whether
the ASCI ought to admit PhDs (100). In 1993 an
ASCI committee explicitly addressed whether non-MDs ought to become eligible for ASCI
membership and concluded that they should not. Instead, they suggested, PhDs could
become honorary members. Further discussion revealed some strong voices in favor of
allowing PhDs to become regular members. The JCI editorial staff liked
the idea, feeling that it might increase submissions from PhDs. Witnessing a decline in
interest and nominations, some went so far as to suggest that admitting PhDs
“might save the society from eventual extinction.” It was noted
that clinical specialty groups treated non-MDs as equals. Some suggested that the
current practice led to a double standard — PhDs could give plenary talks
yet couldn’t be members. Those in opposition to changing the basis for
admission noted that allowing PhDs would lead to more work for the Council and, perhaps
most significantly, could change the ASCI character. After a 1997 survey showed only
5.7% of ASCI members in favor of electing non-MDs, the matter appears to have largely
died down.

America has long grappled with the issue of women in medicine. Only in 1849 did
Elizabeth Blackwell become the first woman to graduate from a US medical school; in 1870
the University of Michigan became the first major medical school to admit women. During
the early 20th century, a few women gained admission to many formerly all-male medical
schools, yet as previously all-female schools closed, the numbers of women in medicine
declined (101–103). Prominent leaders discouraged women from entering medicine,
including Yale’s Medical School dean and ASCI president George Blumer. In
his nationally noted 1918 address, “Medical Education in Relation to the
War,” Blumer, concerned about the toll the First World War was taking on
medical school faculty, feared that “the decimated ranks of teachers must be
filled by women, cripples, and dotards” (19). By explicitly linking women with “cripples and
dotards,” he was clearly stating that he did not see women as desirable
members of the (or his) medical school faculty. (Nonetheless, Yale was among the leaders
during this period in training women scientists; ref. 104.) That Blumer chose to make his remarks just as women were trying to gain
the right to vote (which they did upon the 1920 ratification of the 19th amendment to
the US Constitution) was doubtless not lost on his audience.

During the first part of the 20th century, only a few women were elected to membership
in the ASCI, in modest numbers that mirrored the general difficulty women had in
succeeding in any medical or scientific field. The situation started to change following
the early 1970s passage of “equal opportunity” amendments to the
Civil Rights Act, as female applicants to medical school more than tripled. In 1976, the
Association of American Medical College data directed attention to the gender gap in US
medical school faculties. In this climate of increased attention to women, ASCI member
Phyllis Bodel urged the Council to try to increase the nomination and election of women.
Bodel was a Yale internist who strove to improve professional opportunities for women
both locally and nationally; she died from leukemia only one year after meeting with the
ASCI Council, at the age of 44 (105). After her
meeting with the Council, the numbers of women admitted to the ASCI started to increase.
During the years 1969–1978, only 2.4% of people elected to ASCI membership
were women. That percentage nearly doubled over the next ten years, to 4%. Today, as the
ASCI reaches the end of its first century, while medical schools are approaching a 50:50
gender split, only about 15% of those elected to ASCI membership are women. One obvious
route to future ASCI membership is through medical scientist training programs. They are
nearing a 50:50 gender divide, albeit more slowly than medical schools at large.
However, there is greater attrition for women than men in these programs, and the number
of women in senior positions still lags (106–108).

The initial ASCI members were quite young, many in their early thirties. Election to
ASCI membership has been restricted to people under the age of 45. Suggestions have been
made both to lower this age requirement and to raise it; the latter suggestion is based
in part on the fact that some physician-scientists have career tracks that are
interrupted by family obligations, and those people are disproportionately women.
Despite several formal reviews of the age requirement, it has not been changed. In 1930,
the ASCI decided that members who reached the age of 45 would become emeritus. Today
members acquire senior status at age 51 and are eligible for emeritus status at age 65.
The intent has remained the same, that the society be made up of relatively young
members.

We do not have reliable data on ethnicity and ASCI membership, but it is unlikely that
the ASCI has been any better than medical school faculties at large in recruiting
members of underrepresented minorities. In 2002, only 6% of those receiving PhDs in the
biomedical sciences were from underrepresented minorities (109). Other criteria once used for membership have largely
disappeared. For many years, prominent medical schools used quotas to cap the number of
people with specific religious or ethnic backgrounds (110, 111). As late as 1939, T.R.
Harrison noted in his ASCI presidential address that religion was often used as a marker
for appointment to societies and academic posts (112). On the whole, the ASCI has probably mirrored the larger profession in
accepting non-majority members.

While a history of the changing scientific methods that have been used to advance
“clinical research” lies beyond the scope of this article, a
persistent question for the ASCI has been whether nonbiological research ought to
qualify someone for membership. Recall Haven Emerson, whose 1909 scientific
presentation, the very first ever to an ASCI meeting, was based on a high-technology
diagnostic tool. Emerson was a leader in the small group of physicians who were shaping
remarkable changes using experimental physiology to study medicine. However, by the time
Emerson became ASCI president in 1917, he was New York City Commissioner of Health and
had turned his scientific research interests away from the bench sciences to public
health and epidemiology. His 1917 ASCI presidential address, “The Community
as a Patient Needing Clinical Investigation,” reflected his shift in
research focus and may mark the first intimation of serious population-based research in
the ASCI. Emerson went on to a distinguished career as an epidemiologist, a founder of
the American Epidemiological Society, and a president of the American Public Health
Association (113–115). While his turn to a population-based research
model might later be seen as suggesting a public health orientation, in 1917 the gap
between public health and medicine was much smaller than it is today, and this sort of
research was well accepted in the medical school world (116).

In 1938 John Paul, a distinguished scientist who provided fundamental insights into
poliomyelitis, devoted his ASCI presidential address to the subject of clinical
epidemiology, which he saw as “a new science . . . in which this new Society
might take an important part.” Paul pleaded for the ASCI to take a broad
view of research methods: “Of late years conservative opinion does not allow
anything to be really considered as ‘etiology,’ unless we can
succeed in getting it into a test tube, unless we can precipitate it —
unless we can crystallize it as it were. This is due of course to our current
methodology which has, perhaps, become more of a religion than most of us realize. I
think it may have led to a slightly narrower interpretation of clinical investigation on
our part, for clinical investigation certainly should be given the opportunity to spread
itself up into philosophy, if it will, as well as down into the basic
sciences” (117). A few years later,
the editors of the JCI agreed with Paul, decrying the cult of the new
scientific tools and wishing for a new emphasis on “emotional, social, and
economic factors in human sickness” (118).

Voices calling for a more catholic interpretation of the meaning of clinical research
were largely washed away by the postwar torrent of NIH funds and the demonstrable
achievements of the basic biological sciences. During the latter half of the 1960s,
health services research became a more established investigative method. In 1971 ASCI
president Halsted Holman recognized the “importance of rigorous and
imaginative research and experimentation in health care delivery” and
proposed that the ASCI establish a regular section as a way to foster such research.

It didn’t happen. Some members were not so sanguine as Holman about
accepting ASCI members based on nonbiological research. Compared with the traditional
sciences, health services and outcomes research could be seen as less scholarly and more
ideological. In the turbulent 1970s, members feared that people working in these fields
would politicize the ASCI. Another issue was how to judge the quality of nonbiological
research, since most ASCI members were unfamiliar with its techniques. One suggestion
was an ad hoc committee to review such applicants, but others feared that such an
approach could be the “camel’s nose under the tent,”
leading to an organized constituency that might eventually become a dominant force in
the ASCI. In 2001 ASCI president David Ginsburg suggested that one way for the ASCI to
acknowledge the different scholarly traditions was to reorganize into two sections
— one laboratory based, one not (David Ginsburg, personal communication).
This suggestion was not acted on. Today, the ASCI admits a few members based on
nonbiological research, but the vast majority continue to do clinical research using
methods drawn from the laboratory-based sciences.

Should the ASCI do anything besides its original goal of selecting new members and
holding an annual meeting? Answers to this question have varied throughout the years.
The ASCI has occasionally attempted some sort of outreach. From 1991 to 1997, it offered
a program designed to give high school teachers the chance to spend time in a science
laboratory, but it discontinued support because the program was not seen as central to
the ASCI’s goals and objectives.

Ever since 1924, publishing the JCI has been one of the
ASCI’s most important activities. After surviving the difficult first few
decades, the journal has prospered, in large part because it has embodied elements of
both continuity and change. Research reported in the JCI has reflected
the latest trends in biomedical research. A detailed content analysis lies beyond the
scope of this paper, but a retrospective on the occasion of the
JCI’s 80th anniversary includes commentaries on notable
publications (119, 120). Since the JCI has sought to publish
original, innovative papers, it is perhaps not surprising that some medical
practitioners have questioned the relevance of those articles for clinical care. Nor are
these concerns new. The plaintive comments that “there is nothing very
clinical about the JCI any more” have been heard for more than half a
century (121, 122). Currently, about one of three of JCI papers accepted
or returned for revision reports work done with humans or with human tissue
— whether this percentage is too high, too low, or about right will depend
on the reader’s perspective (123).

The JCI’s editorial staff and institutional home now move
every five years. These moves have offered the opportunity for change. At its most
recent editorial transition, the JCI named an associate editor who
focuses on clinical epidemiology. Relatively new sections include editorials, book
reviews, review articles, and, most recently, a section on “Technical
Advances.” The journal has itself embraced technical changes, although in
1977 color photography was only adopted over the objections of an editor who initially
thought the idea “outlandish” (124). In 1996 the JCI became the first major scientific
journal to be available free on the Internet, and in 2004 the layout was redesigned to
be more useful for the increasing number of readers who read the JCI
only on the Internet (125). After a rough start,
the JCI does well enough financially to be a source of support for ASCI
activities. The JCI has been self-publishing since 1999. Its climbing
impact factor (less than 11 in 2001, now over 16) reflects the high standing in which it
is held. Joseph Goldstein and Michael Brown aptly described the special importance of
the JCI — its readers are a broad group (broader than the
readership of most specialty journals) but also a group more attuned to clinical
relevance than most readers of other high-profile general scientific journals (124).

A final set of questions revolves around whether the ASCI should try to influence
policy. Initially, the question seems not to have been explicitly asked, and the ASCI
simply took a policy position whenever a majority of the members wanted to do so. For
example, in 1917, as the United States pondered a constitutional amendment prohibiting
the sale of alcoholic beverages, the ASCI weighed in on this important issue by passing
a resolution saying “That in the critical condition of the
world’s food supply, we consider it desirable that the manufacture of
alcoholic beverages or their importation into this country be prohibited for the
duration of the war and for at least one year thereafter.” (Available
records do not document whether there was a significant reduction in the consumption of
alcoholic beverages at ASCI meetings after passage of this resolution or after the 1919
ratification of the amendment.) Another example of an ad hoc policy position was
endorsement in 1926 of the “aims and activities of the American Association
for Medical Progress,” an organization made up of prominent academics and
civic leaders to support science, especially animal experimentation (126).

In 1950, as federal support of scientific research was rapidly rising, the ASCI Council
started explicitly to discuss the possibility of the ASCI taking a policy position on
federal research support. They initially felt that individual members should not make
their personal opinions known through the ASCI but instead “through other
societies, their own institutions, or boards and committees on which they
serve,” an approach that would lead perforce to lobbying efforts that were
scattered and uncoordinated. Perhaps as a result of the increasing dependence of ASCI
members on federal research funds, perhaps as a response to public criticisms of
biomedical research, starting in the 1960s the ASCI as a society started to take policy
positions on issues involving biomedical research funding (127). Sometimes the stand opposed onerous quarterly reporting
requirements, sometimes the Council argued against limiting changes in the direction of
funded research. In 1970 ASCI representatives were encouraged to testify before Congress
that basic research (italics in original) would save money. Subsequent
years were marked by both discussion of research grant policy and concerns that the ASCI
is a “politically powerless” organization (128). A 1997 survey revealed that nearly 80% of ASCI members wanted
the society to take stands on public policy.

In support of that goal, in 1998 the ASCI became the 12th full member of the Federation
of American Societies for Experimental Biology (FASEB), hoping that FASEB would enable
policy makers to hear not a cacophony of small requests, but one consensus voice. The
ASCI worked with FASEB to enhance the NIH budget and to support physician-scientists,
especially physicians in clinical research, who since 1979 had been labeled an
“endangered species” (129). Hoping to encourage more people to remain in academic positions, the ASCI
and FASEB helped to craft a loan repayment program. But despite the national salience of
science and scientific research, science policy continues to receive scant attention in
national policy debates (130).

It is hardly surprising that the ASCI of 2009 is very different from that of 1909. The
fundamental tenets of clinical research, its definitions, techniques, and traditions,
have all undergone the sorts of profound transitions and transformations one would
expect over the course of 100 years (Figure 9).
Likewise, the social context in which the ASCI exists has also changed dramatically.

Yet something else has changed. One hundred years ago, the first ASCI meeting brought
together a group of revolutionaries trying to establish a new model for doing clinical
research. They succeeded. They won. Over the course of the century, the Young Turks have
become the status quo. Today, in 2009, the ideas that provided the impetus for change
have become mainstream. The “Sultan has crept back into the
palace” (131). Rather than being a
marker for radical transformation, the ASCI has become a marker for academic success.
Again, this transformation is hardly surprising. Revolutionary movements, in whatever
field, rarely persist as revolutionary over the course of a century. They either succeed
or die. And the ASCI did not die.

But it has changed, and it will continue to change. What will the ASCI be like a century
hence? Will it be a home for innovative and creative challenges to established
orthodoxy? Or will it be a means of sustaining the status quo? Answering these questions
requires a different set of disciplinary skills — history is not prophecy.
But history does serve to remind us, first, that the world will change, that established
notions about what defines science and scientific excellence have changed and will
continue to change. Historical analysis also reminds us that the ASCI will continue to
reflect the changing social, political, and economic context in which it exists and to
suggest some of the questions that will continue to be asked about the society.

Notes on sources. Much of the narrative description comes from the administrative records of the
society, the Secretary’s Book, Council Minutes, and records of the annual
meetings. Records from 1907 to 1977 are located in the History of Medicine Division
of the National Library of Medicine, Bethesda, Maryland, USA. More recent records are
housed at the ASCI national office, Ann Arbor, Michigan, USA. Some of this material
is paginated; most is not. Specific citations are provided only if the source
(Council minutes, committee reports) is not located in the chronologically ordered
archival administrative records. Other useful archival records are to be found in
various holdings of the Rockefeller Archive Center, Sleepy Hollow, New York, USA. The
entire run of the JCI — including the 50th-anniversary
history of the ASCI (66), with much more
detail on many topics — is available free online at
http://www.jci.org/archive.

I appreciate careful readings and discussions of the manuscript by David Ginsburg,
Halsted R. Holman, Powel Kazanjian, William N. Kelley, and Sanjay Saint. Staff at the
History of Medicine Division of the National Library of Medicine and the Rockefeller
Archive Center were extremely helpful. Toby Appel provided assistance in obtaining
information about Phyllis Bodel. Writing of this paper was supported by a grant from the
American Society for Clinical Investigation.

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